EGFR is a receptor recognizing an epidermal growth factor, that controls cell proliferation and growth and transmitting signals, and plays an important role in cellular functions such as cell proliferation, differentiation and migration. According to signals from the EGFR, cell proliferation is promoted, apoptosis is suppressed, and mobility of tumor cells and new blood vessel growth are increased. EGFR functions in tumor specific manner, and its high expression is observed within a wide range of tumors in human epithelial tissues including non-small-cell lung cancer (NSCLC), breast cancer, squamous cell carcinoma of the head and neck (SCCHN), stomach cancer, colon cancer, esophageal cancer, prostate cancer, urinary bladder cancer, kidney cancer, colon cancer, and ovarian cancer.
According to these discoveries, EGFR is recognized as an important target for a delivery system mediating between a drug and a receptor of a gene in a cancer treatment. However, EGF, that is a ligand of EGFR, remarkably enhances mitotic division and angiogenesis, and it is therefore important to find a substrate such as EGF. A peptide ligand which can be easily diffused and shows low immunogenicity, and also can easily take in a gene transportation vector, has been studied as a target site for selectively delivering radionuclides, cytokines, chemical drugs, and therapeutic genes to a tumor. Recently, a research result of obtaining a peptide ligand by use of phage library screening has been reported (Non-Patent Document 1).
On the other hand, a receptor protein belonging to an EGFR family member is one of the best-characterized targets of cancer cells. The EGF family including EGFR known as HER1 or ErbB1, HER2 known as ErbB2 or neu, HER3 (ErbB3) and HER4 (ErbB4) is important in cell survival, differentiation and proliferation. In particular, when EGFR signal is increased, it associates with carcinogenic transformation. As a result, independent cell survival, tumor invasion, new blood vessel growth and metastasis are induced. Expression of EGFR and high expression thereof have been reported in various tumor types, a high expression level of EGFR in one third of epithelial cancers has been known, and high expression of EGFR is frequently associated with adverse prognosis. Furthermore, EGFR is known to be related to generation and growth of cancer, and drugs for chemotherapy targeting EGFR have been developed. Cetuximab (IMC-C225, Erbitax) which is one of inhibitors of EGFR is a monoclonal antibody approved as a therapeutic agent for metastatic colon cancer by FDA. Cetuximab is a human-mouse chimeric antibody and targets an extracellular domain of EGFR. Cetuximab binds to EGFR with higher affinity than EGF and a TFG-α that are original ligands and competitively inhibits binding to EGFR to suppress the activity (Non-Patent Document 2, Patent Document 1). Another example of a human anti-EGFR monoclonal antibody includes panitumumab (Vectibix (registered trademark)) (Patent Document 2).